Brønsted Acid-Catalyzed Three-Component One-Pot Regiospecific Synthesis of Functionalized N -Fused 6-Aryl- N -aryl-imidazo[2,1- b ][1,3,4]thiadiazol-5-amine and 5-Aroyl-5,7,8,9-tetrahydro-6 H -[1,3,4]thiadiazolo[2,3- b ]quinazolin-6-one: N - vs C -Nucleophile Control Selectivity Switch between [5,5]- and [5,6]-Membered Bicyclic Cores

A metal-free organocatalytic one-pot three-component reaction strategy of electron-poor 2-amino-1,3,4-thiadiazole, N -nucleophilic aromatic amine, and arylglyoxal monohydrate synthesizing functionally rich N -fused [5,5]-membered 6-aryl- N -aryl-imidazo[2,1- b ][1,3,4]thiadiazol-5-amine has been devised in the presence of catalytic TsOH·H 2 O under refluxing EtOH and microwave heating as two separate operations. Replacing the aromatic amine with a C -nucleophilic cyclic 1,3-diketone, 1,3-cyclohexanedione, furnished functionally rich N -fused [5,6]-membered 5-aroyl-5,7,8,9-tetrahydro-6 H -[1,3,4]thiadiazolo[2,3- b ]quinazolin-6-one under both conditions. The selectivity switch between N -fused [5,5]-membered and [5,6]-membered heterocyclic cores could be regulated through the identity of nucleophiles ( N - vs C -nucleophiles) used. The nonconventional microwave irradiation provided a faster rate of reaction compared to conventional EtOH reflux. A broad substrate scope with respect to structural and electronic variations of the reaction components enables the generation of diverse final products in a regiospecific manner. Operational simplicity, excellent product yields, exclusive regioselectivity, use of the environmentally friendly EtOH solvent, absence of byproducts involving nucleophilic EtOH as a reaction constituent, “gram-scale” production, and synthetic modification of the end product are distinct advantages of the prescribed protocols. The interception or isolation and characterization of several reactive intermediates allow us to elucidate the mechanistic courses of the reaction pathways reasonably.